糖尿病患者血浆血栓素A_2、前列环素、内皮素水平变化及临床意义

目的:探讨糖尿病合并血管并发症患者血浆血栓素A2(TXA2)、前列环素(PGI2)和内皮素(ET)水平的变化。方法:应用放射免疫法测定56例糖尿病患者和30例正常人血浆TXA2、PGI2和ET水平。结果:有血管病变糖尿病患者较无血管病变糖尿病患者血浆TXA2明显升高,PGI2明显降低,血浆ET明显升高。结论:TXA2—PGI2平衡失调和血浆ET升高在糖尿病血管病变的发病机制中可能起重要作用。     

六味地黄方对高脂血症大鼠血浆 ET、TXA2、PGI2水平及动脉内皮保护的影响

目的：研究六味地黄方对高脂血症大鼠血浆ET、TXA2、PGI2水平及动脉血管内皮保护的影响。方法：通过高脂饮食建立高脂血症大鼠模型,观察大鼠外周循环内皮细胞（CEC）、主动脉病理学、内皮素（ET）、前列腺素I2（PGI2）、血栓素A2（TXA2）的变化。结果：六味地黄方能减少高脂血症大鼠外周CEC及主动脉内皮细胞损伤;降低高脂大鼠血清ET、血浆TXA2,升高血浆PGI2水平。结论：六味地黄方对高脂血症大鼠内皮细胞具有保护作用,其作用机制可能与改善内皮细胞分泌功能有关。     

复方丹参滴丸对动脉粥样硬化患者血管内皮细胞分泌功能的影响

目的研究复方丹参滴丸对血管内皮细胞分泌功能的保护作用,探讨其机制。方法选择动脉粥样硬化患者200例,入选患者实验前采空腹静脉血检测ET、PGI2、TXA2,然后给与复方丹参滴丸10丸/次,3次/d,服用3个月,再采空腹静脉血检测ET、PGI2、TXA2,自身前后对照研究。结果患者实验前的ET、TXA2明显较高,而PGI2水较低,而给与复方丹参滴丸干预后再检测ET、PGI2、TXA2,服药前相反,ET、TXA2明显降低（P〈0.01）,而PGI2明显升高（P〈0.01）。结论复方丹参滴丸能够调整、改善血管内皮细胞分泌功能的异常状态,血管内皮细胞可能是复方丹参滴丸作用的靶点之一。     

盐酸川芎嗪注射液对慢性肺心病患者血浆TXA2、PGI2影响的动态观察

目的：观察在应用抗生素的基础上,联合盐酸川芎嗪注射液治疗慢性肺心病,动态观测血浆TXA2、PGI2水平改变对肺动脉压力的影响,从而评估盐酸川芎嗪注射液对肺心病患者的治疗作用和价值。方法：测定3组药物治疗前、中、后血浆血栓素A2（TXA2）、前列环素（PGI2）水平,以及血气指标。结果：肺心病患者在急性发作期血浆TXB2水平升高,6-K-PGF1α水平降低,TXB2/6-K-PGF1α比值升高,与对照组比较差异显著（P〈0.001）。提示肺心病患者在急性发作期存在着TXA2-PGI2平衡失调;川芎嗪具有降低TXA2、升高TPI2水平的作用,并导致肺动脉压下降,如将川芎嗪和氨茶碱联合应用,其血浆TXB2、6-K-PGF1α水平改变更为显著。此外,盐酸川芎嗪注射液在降低PaCO2的同时,还能改善组织供氧状态。结论：我们认为盐酸川芎嗪注射液有降低TXA2、升高TPI2水平,并导致肺动脉压下降的作用,其用药安全,不良反应小,且价格低廉。临床上有进一步积累资料深入研究和推广应用的价值。     

固脱汤对失血性休克大鼠血浆NO、6—keto—PGF1α和TXB2含量的影响

目的和方法：观察固脱汤对失血性休克大鼠血浆NO、6－keto-PGF1α和TXA2含量的影响。结果：失血性休克大鼠血浆NO水平增高（P＜0．01），6－keto－PGF1α含量明显降低（P＜0．01），TXA2含量增高（P＜0．01），固脱汤加可明显升高血浆NO、6－keto-PGF1α水平（P＜0．01），而血浆TXB2含量未见显著性改变（P＞0．05）。结论：固脱汤可通过促进血管内皮细胞产生和释放NO及PGI1发挥抗休克作用。     

梗阻性黄疸患者空肠粘膜组织前列环素、血栓素、还原型谷胱甘肽含量测定的意义

目的 探讨空肠粘膜前列环素（PGI2），血栓素（TXA2），还原型谷胱基肽（GSH）含量的变化在梗阻性黄疸（OJ）患者肠粘膜屏障功能损伤中的意义。方法 采用放免法测定12例OJ和8例胃窦部良性溃疡（GU）患者空肠粘膜组织PGI2，TXA2含量。采用分光光度法测定空肠粘膜组织GSH含量。结果 OJ组空肠粘膜组织PGI2，GSH含量较GU组明显降低，TXA2明显升高。结论 OJ患者空肠粘膜组织PGI2，GSH降低及TXA2含量升高与其粘膜损伤及屏障功能障碍相关。     

丹参注射液对妊娠高血压综合征患者血浆TNF-α和TXA2／PGI2平衡的调节作用

目的观察丹参注射液治疗前后妊娠高血压综合征(PIH)患者血清TNF-α变化和血浆血栓素A2(TXA2)/前列环素(PGI2)平衡变化情况,探讨其治疗PIH的作用机制。方法选择40例轻中度PIH患者,予以丹参注射液8mL静滴10d(丹参治疗组),同时另取正常妊娠40例做对照。ELISA双抗体夹心法检测丹参治疗组治疗前后TNF-α的含量变化,放射免疫法测定治疗前后血浆中TXA2、PGI2其稳定代谢产物TXB2和6-keto-PGF1α的浓度作为判断TXA2和PGI2含量的指标;同时测定正常妊娠对照组的TNF-α、TXB2和6-keto-PGF1α的含量作为比较。结果与正常妊娠对照组相比较,治疗前丹参治疗组患者血清TNF-α含量升高(P<0.05);血浆TXA2含量升高(P<0.05),而血浆PGI2含量降低(P<0.05),TXA2/PGI2比值升高。经过丹参注射液治疗10d后,与治疗前相比较,血清TNF-α含量有所下降(P<0.05);血浆TXA2含量有所下降(P<0.05),血浆PGI2含量有所上升(P<0.05),TXA2/PGI2比值下降。结论PIH病程中存在TNF-α水平升高和TXA2/PGI2比值升高。丹参治疗PIH的作用机制可能是通过降低患者血清TNF-α含量,使血管内皮通透性恢复;同时纠正血管活性物质分泌失衡,使血浆TXA2含量下降,血浆PGI2含量上升,TXA2/PGI2比值失衡恢复,最终使妊娠高血压综合征病程得以逆转。     

丹参注射液对妊娠高血压综合征患者血浆TNF-á和TXA2/PGI2平衡的调节作用

目的 观察丹参注射液治疗前后妊娠高血压综合征(PIH)患者血清TNF-α变化和血浆血栓素A2(TXA2)/前列环素(PGI2)平衡变化情况,探讨其治疗PIH的作用机制.方法 选择40例轻中度PIH患者,予以丹参注射液8mL静滴10d(丹参治疗组),同时另取正常妊娠40例做对照.ELISA双抗体夹心法检测丹参治疗组治疗前后TNF-α的含量变化,放射免疫法测定治疗前后血浆中TXA2、PGI2其稳定代谢产物TXB2和6-keto-PGF1α的浓度作为判断TXA2和PGI2含量的指标;同时测定正常妊娠对照组的TNF-α、TXB2和6-keto-PGF1α的含量作为比较.结果 与正常妊娠对照组相比较,治疗前丹参治疗组患者血清TNF-α含量升高(P＜0.05);血浆TXA2含量升高(P＜0.05),而血浆PGI2含量降低(P＜0.05),TXA2/PGI2比值升高.经过丹参注射液治疗10d后,与治疗前相比较,血清TNF-á含量有所下降(P＜0.05);血浆TXA2含量有所下降(P＜0.05),血浆PGI2含量有所上升(P＜0.05),TXA2/PGI2比值下降.结论 PIH病程中存在TNF-α水平升高和TXA2/PGI2比值升高.丹参治疗PIH的作用机制可能是通过降低患者血清TNF-α含量,使血管内皮通透性恢复;同时纠正血管活性物质分泌失衡,使血浆TXA2含量下降,血浆PGI2含量上升,TXA2/PGI2比值失衡恢复,最终使妊娠高血压综合征病程得以逆转.     

银杏黄酮磷脂复合物对大鼠心肌再灌注血管内皮损伤的保护作用

目的:探讨银杏黄酮磷脂复合物对大鼠心肌缺血再灌注血管内皮损伤的保护作用。方法:健康Wister大鼠40只,随机分为假手术组、模型组、银杏黄酮组及银杏黄酮磷脂复合物组,每组10只,检测各组血浆内皮素(ET1)、前列环素(PGI2)、血栓素A2(TXA2)水平及血清一氧化氮(NO)、丙二醛(MDA)水平和超氧化物歧化酶(SOD)活性。结果:银杏黄酮磷脂复合物对心肌缺血30min再灌注120min大鼠,可明显降低血清NO及MDA含量,而使SOD活性增强,亦使血浆ET1、TXA2水平下降,PGI2水平及PGI2/TXA2比值明显增高,且变化较银杏黄酮显著。结论:银杏黄酮磷脂复合物对大鼠心肌再灌注血管内皮损伤具有明显的保护作用,可能与其增强抗氧化酶活性,减少自由基对内皮细胞的氧化损伤,减少内源性血管活性物质ET1释放,纠正PGI2/TXA2失衡等机制有关。     

氯沙坦与非洛地平的降压疗效及对血管内皮功能影响的对比观察

为探讨氯沙坦的降压疗效和对血管内皮功能的影响，对60例高血压病患分别应用氯沙坦和非洛地平治疗进行对比观察。记录每日血压和24h动态血压变化。取静脉血测定治疗前后血浆一氧化氮（NO）、前列环素（PGI2）、内皮素（ET）、血管紧张素Ⅱ（AngⅡ）水平。结果显示，氯沙坦的降压疗效明显，但同非洛地平相比较，二无显性差异（P＞0．05）：氯沙坦组血浆NO、PGI2、AngⅡ升高，ET降低。结论：氯沙坦是一种安全有效的降压药，可以改善高血压患血管内皮功能.     

Trifluoperazine plasma levels and clinical response

The authors studied 36 acutely psychotic inpatients who were diagnosed as having either a schizophrenic (N = 30) or other psychotic (N = 6) disorder. After a washout phase averaging 18 days, all patients were placed on trifluoperazine 5 mg orally twice a day. Plasma levels of trifluoperazine were obtained on days 11 and 15 of treatment and then compared with clinical response. After 2 weeks of treatment an inverted U-shaped relationship was found between change scores on the Brief Psychiatric Rating Scale and trifluoperazine plasma levels.     

Fluphenazine plasma levels and clinical response

We monitored fluphenazine plasma levels in 39 schizophrenic patients who participated in a 2-year double-blind comparison of 5 mg and 25 mg of fluphenazine decanoate (FD) administered every 14 days. We investigated the relationship between log-transformed plasma levels at 3, 6, and 9 months and subsequent psychotic exacerbations with logistic regression and survival analysis. Using logistic regression, the relationship was nonsignificant at 3 months (chi-square = .21, df = 1, p = .65), but significant at 6 months (chi-square = 4.38, df = 1, p = .04) and 9 months (chi-square = 8.98, df = 1, p = .003). Using survival analysis with fluphenazine levels as a covariate (Cox models), we also found significant relationships between the fluphenazine plasma level and the risk of exacerbations at 6 months (chi-square = 3.77, df = 1, p = .052) and 9 months (chi-square = 12.21, df = 1, p = .0005), but not at three months (chi-square = 0.87, df = 1, p = .65). These findings suggest that the measurement of fluphenazine plasma levels may be helpful in decision-making about the dosage of FD.     

Biperiden effects and plasma levels in volunteers

Summary The pharmacokinetics of biperiden was studied and compared with pharmacodynamics (pupil size, accomodation, self-rating mood scale) in 6 healthy volunteers. A single-blind cross-over design was employed with placebo and biperiden (4 mg as commercially available tablets). After a lag time of 0.5 h, biperiden was rapidly absorbed with a half-life of 0.3 h, plasma peak levels of 5 ng/ml being reached after 1.5 h. Biperiden showed good tissue penetration (distribution half-life 0.6 h; ratio of total to central distribution volume 9.6), the terminal half-life time of plasma concentration was 18 h, and the oral clearance was 146 l/h. The pharmacodynamic maximum lagged behind the plasma peak concentration by 1 (self-rating) to 4 h (accommodation).Dedicated to Prof. Dr. Ernst Biekert on the occasion of his 60th birthday     

Impairment of memory and plasma flunitrazepam levels

 The 5-HT_2A/2C receptor antagonist, ritanserin, was reported to retard the acquisition of conditioned responses (CRs) during classical conditioning of the rabbit’s nictitating membrane (NM) response. The present study compared the effects of ritanserin on acquisition of CRs to a tone conditioned stimulus (CS) with that of the 5-HT_2A/2C receptor antagonist, LY-53,857 and the 5-HT_2A selective antagonist, MDL-11,939. All three drugs were injected at equimolar doses of 0.067, 0.67 and 6.7 μmol/kg, SC, 1 h before behavioral testing. Ritanserin and MDL-11,939 retarded CR acquisition to a tone CS, while LY-53,857 had no effect. Control experiments demonstrated that ritanserin (1 μmol/kg), MDL-11,939 (1 μmol/kg) and LY-53,857 (2 μmol/kg) had no effect on baseline responding or non-associative responding to the CS. However, both ritanserin and MDL-11,939 impaired the performance of the unconditioned NM reflex, as measured by a decrease in UR amplitudes on US alone trials, while LY-53,857 had no effect. In previously trained animals, ritanserin robustly impaired the performance of CRs, as measured by a reduced ability of the CS to elicit CRs, while the effects of LY-53,857 and MDL-11,939 were marginal. The retardation of associative learning produced by ritanserin and MDL-11,939 may have been due, at least in part, to their impairment of the NM reflex arc. Since MDL-11,939 is a highly selective 5-HT_2A antagonist, the retardation of learning and impairment of UR amplitudes produced by MDL-11,939 and ritanserin may have been due to blockade of the 5-HT_2A receptor. The ability of ritanserin and MDL-11,939 to produce effects on learning and performance that were opposite to that of 5-HT_2A/2C agonists suggests that they may be acting as inverse agonists at that receptor. These results stress the importance of the serotonergic system for optimal associative learning and motor function. Received: 22 May 1997 / Final version: 3 December 1997     

Clonidine reduces plasma melatonin levels

Clonidine, an alpha-adrenoceptor agonist, reduces human plasma melatonin levels when administered intravenously at 2-3 micrograms kg-1 to sleeping volunteers. Measurement of plasma melatonin levels after administration of clonidine could be the basis for a clinical in-vivo test of alpha-adrenoceptors.